In 2017 the Retroviral Immunology Section continued investigation into host mechanisms of genetic resistance and susceptibility to retroviral infection. These findings have implications for the design of therapeutics and vaccines to treat and prevent infections with viruses such as HIV. Studies of Friend retrovirus-infected mice revealed a completely new role for B cells outside of their normal antibody-producing and antigen presentation functions. We found that B cells were absolutely required for the induction of regulatory T cell (Treg) responses during infection. Such Treg responses are critical for preventing immunopatholgical damage by overactive immune responses to infectious agents. Experiments showed that a cell surface molecule (GITR-L) expressed on B cells bound to a protein on Tregs (GITR) and delivered an activation signal that allowed the Tregs to respond. In the absence of that signal, the Tregs responded poorly (Moore et al. Bio 2017). Experiments in the Friend virus model of retroviral infections also showed how Tregs were involved in suppressing cytolytic activity by CD4+ T cells. It was shown that CD4+ T cell killing of virus-infected cells could be enhanced by immunotherapy that combined inactivation of Tregs and costimulation of CD4+ T cells via CD137 (Malyshkina et al. Scientific Reports 2017). Further experiments studying immunity in the Friend virus model showed that restriction of virus replication by APOBEC3-mediated virus-neutralizing antibody responses was dependent on type I IFN signaling, but that type I IFN signaling was not required for direct, innate restriction by APOBEC3. These experiments demonstrated that APOBEC3 suppresses virus replication and spread through at least 3 separate mechanisms that operate through distinct pathways (Barrett et al. Retrovirology 2017). One of the interesting ways an infected cell restricts spread of virus is by a molecule called Tetherin/BST-2 that tethers nascent virions to the plasma membrane. Using the Friend retrovirus model, we demonstrated that Tethering also enhanced the activation of dendritic cells and strengthened Natural Killer cell responses. Furthermore, Tetherin+ dendritic cells from FV-infected mice more strongly stimulated virus-specific CD4+ T cells compared to Tethering knockout DCs. The results link the antiretroviral and immunomodulatory activities of Tetherin in vivo to improved DC activation and MHC class II antigen presentation (Li et al. Journal of Immunology 2016). Knowledge and tools developed in studies on Friend virus were used to contribute to investigation into immunity against ZIKA virus infection of mice. These studies illustrated that, in addition to innate immunity, contributions from adaptive immunity, such as antibody responses and T cell responses, were also important. Furthermore, we demonstrated that pregnancy diminished the adaptive immune responses, likely leading to increased infection of the fetus (Winkler et al. Journal of Immunology 2017).